This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Currently, use of basal and total cortisol concentrations are the only tools available to diagnose adrenocoritical insufficiency. However, serum cortisol is significantly bound to cortisol binding globulin and albumin. In critically ill patients, cortisol binding is markedly diminished. Thus, reduced basal and stimulated total cortisol levels in critically ill patients are predominantly due to reduced cortisol binding with only a small percentage having adrenocortical insufficiency and requiring gluccocorticoid replacement therapy. Basal serum free and total cortisol, salivary free cortisol, cortisol binding globulin (CGB), albumin and ACTH levels will allow assessment of cortisol binding and the hypothalamic-pituitary-adrenal axis, and differentiate patients with cortisol binding from those with adrenocortical insufficiency. Cosyntropin stimulation testing will be done to determine adrenal responsiveness to exogenous ACTH. Alterations in the pituitary-adrenal axis and in cortisol binding will be correlated with parameters indicating the severity of illnesses, specific disease states, drug therapies and outcomes. Studies of patients with a low risk for adrenocortical insufficiency will allow us to determine the appropriate ranges of values for serum and salivary basal and stimulated free cortisol. Studies of high risk patients will allow detemination of the frequency and the characteristics of the patients most likely to have adrenocotical insufficiency. These studies will totally change the way that adrenocortical insufficiency is diagnosed and treated in critically ill patients.